Regional mechanics determine collagen fiber structure in healing myocardial infarcts.

Regional mechanics determine collagen fiber structure in healing myocardial infarcts.
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DOI:
10.1016/j.yjmcc.2012.02.012
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发表时间:
2012-05
影响因子:
5
通讯作者:
Holmes JW
Holmes JW
中科院分区:
医学2区
文献类型:
--
作者:
Fomovsky GM;Rouillard AD;Holmes JW

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心肌梗死后,愈合梗死区的力学特性是心功能和进展为心力衰竭风险的重要决定因素。特别是,愈合梗死的力学各向异性(在不同方向上具有不同的力学性质)可以保持心脏的泵功能。基于不同动物模型中不同胶原结构和力学特性的报道,我们假设梗死大小、形状和/或位置的差异产生不同的机械拉伸模式,从而指导胶原纤维结构的进化。我们使用实验和计算相结合的方法测试了梗死形状和位置的影响。我们对53只Sprague-Dawley大鼠冷冻梗死的力学和胶原纤维结构进行了研究,发现无论形状或方向如何,左心室赤道附近的冷冻梗死主要沿周向拉伸并形成周向排列的胶原,而心尖处的梗死同样沿周向和纵向拉伸并形成随机取向的胶原。在梗死愈合的计算模型中,需要机械拉伸对成纤维细胞和胶原排列的影响来重现实验结果。我们认为机械环境决定了心肌梗死愈合过程中胶原纤维的结构。我们的研究结果表明,改变局部力学的新兴梗死后治疗方法也将改变梗死胶原结构,这既提供了潜在的风险,也提供了新的治疗机会。
Following myocardial infarction, the mechanical properties of the healing infarct are an important determinant of heart function and the risk of progression to heart failure. In particular, mechanical anisotropy (having different mechanical properties in different directions) in the healing infarct can preserve pump function of the heart. Based on reports of different collagen structures and mechanical properties in various animal models, we hypothesized that differences in infarct size, shape, and/or location produce different patterns of mechanical stretch that guide evolving collagen fiber structure. We tested the effects of infarct shape and location using a combined experimental and computational approach. We studied mechanics and collagen fiber structure in cryoinfarcts in 53 Sprague-Dawley rats and found that regardless of shape or orientation, cryoinfarcts near the equator of the left ventricle stretched primarily in the circumferential direction and developed circumferentially aligned collagen, while infarcts at the apex stretched similarly in the circumferential and longitudinal direction and developed randomly oriented collagen. In a computational model of infarct healing, an effect of mechanical stretch on fibroblast and collagen alignment was required to reproduce the experimental results. We conclude that mechanical environment determines collagen fiber structure in healing myocardial infarcts. Our results suggest that emerging post-infarction therapies that alter regional mechanics will also alter infarct collagen structure, offering both potential risks and novel therapeutic opportunities.
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